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Phagocytosis – Inflammation and Wound Repair

Inflammation is the physiologic body reaction in response to injury. The body tries to protect itself from harmful pathogens and physical or chemical irritants. Immune cells, fibroblasts, intra- and extra-cellular mediators are all involved in protecting the body, clearing the inflammatory products and help with the healing damaged parts. Sometimes the whole pathologic disorder is secondary to the body's reaction and inflammation as in cases of hypersensitivity, granulomas and autoimmune diseases. The following article describes various forms of inflammation as well as the body's reaction to them.

00:02
In this picture, with phagocytosis I want you to understand
what's going on in great detail. I want you to beginwith the inset picture on the left, and that is a neutrophil.
Where are you right now in terms of acute inflammation?The neutrophil has left the blood vessel. It has now approached
the bacteria in my interstitium which you call an exudateand we are about to engulf our bacteria. I have taken this
neutrophil the inset and we blown it up in this picture,completely blown it up. I've given you a little area here in
the middle where we are going to swallow and engulf the bacteria.
00:47
If you take a look at that green pellet, it says bacteria. You are
going to take this up, and when you do this is where we begin.
00:57
Your first enzyme you see there is NADPH oxidase. I repeat
NADPH, not NADH. Is that understood from biochemistry.
01:13
You tell me where NADPH is produced in biochemistry.
You've heard of HMP shunt or the hexose monophosphate shuntor pentose phosphate pathway. Lot of P's huh. Can you picture
that. Would you tell me what the rate limiting enzyme isin your HMP shunt. Good. Glucose-6-phosphate dehydrogenase or G6PD.
You must have NADPH so that you can properly form NADPH oxidase.
01:49
So you can take the oxygen. Once again would you tell me what
cell this is. A phagocytic cell, good. And perfectly normalfor a phagocytic cell to create free radicals. I am walking
you through this very methodically because nowwe actually are going to inject pathologies and you may or
may not have seen this pathologies. So there is going to benew information here that you want to be very clear about. Up until
now I have been really quick with the information.
02:21
Now we have created the most important free radical at this point.
This is called a superoxide. You see that superoxide.
02:29
So you have created it. How did you create it? With the help of
NADPH oxidase. Let's stop here for one second. I said pathology.
02:38
What if you have a patient that is deficient of NADPH oxidase.
And you have a child that has recurrent infections.
02:46
Recurrent infections especially to catalase positive organism.
Welcome to chronic granulomatous disease. Right. At some pointI will walk you through a table where I am going to go through
the details of some of these diseases. Let's continue.
03:05
So now you have formed a superoxide. Now you have a next
enzyme. It's called a superoxide dismutase. Perfect.
03:12
And you are going to create another very important component.
That's called H2O2. What's another name for H2O2?Hydrogen peroxide. Very important that you know about hydrogen
peroxide. Let's talk about a few things here. See that iron, Fe,can you tell me a condition in which iron might be overloaded?
Haemochromatosis. What does iron damage? Oh my goodnesseverything in the body. Skin, heart, pancreas, gonads,
everything. How is it causing such damage? You have heard ofFenton reaction. What does that mean? Iron or maybe perhaps
copper may then take the hydrogen peroxideit may create a free radical. And if this free radical is found
outside the neutrophil in excess it's going to cause massivedamage to normal tissue. Are we clear about Fenton reaction.
Let's continue. So now we have formed a hydrogen peroxide.
04:19
In a neutrophil, you take this one step further and you must know
the enzyme MPO, myeloperoxidase. That myeloperoxide will forma very important type of free radical in which it cause ultimate
destruction of this bacteria. Welcome to bleach, amazing huh.
04:39
The inner body, we produce bleach. Unbelieveable. Hypochlorous
acid. This takes care of the bacteria, myeloperoxidase.
04:48
Okay in the meantime, so you have engulfment of a bacteria,
picture that. Just because you engulf something,does it mean that you kill the bacteria? No. Would you tell me
in a neutrophil, it's origin, is called a granulocyte is'nt it.
05:09
What does the granule contain in a neutrophil? These enzymes,
these hydrolytic enzymes. You see them. NADPH oxidase,the myeloperoxidase, okay. So you have taken out the bacteria
but then you have the granule that has to make it's way.
05:27
And then it combines with phagosome and then you form a
phagolysosome. It's only when you have proper fusionof the granule containing the enzyme and this phagosome
containing the bacteria. Kind of like a video game. They combineand once they do, destruction of the bacteria. Simple enough. I know
I was being silly there but it works I hope. Give you another pathology.
05:51
What if the lysosome, the granule does'nt properly make it's
way over to the phagosome. And you don't kill your bacteria.
06:00
What's the name of that disease? Good, that's Chediak Higashi. Two
diseases here right off the bat. NADPH oxidase deficiency,chronic granulomatous disease or don't properly migrate your
lysosome over this then results in Chediak Higashi disease.
06:19
Spend a little bit time. Not to worry I will give you further
details. In the meantime, I want you to take a look at somethingelse here. There is my hydrogen peroxide and by that I mean take
a look at the right side. There is my hydrogen peroxideand with that hydrogen peroxide you will notice that you
have glutathione taking care of that hydrogen peroxide.
06:40
How do you form reduced glutathione, that GSH? You need NADPH. How do
you form that NADPH? The G6PD. Glucose-6-phosphate dehydrogenase.
06:52
I want us to stop here. I am going to give you a third pathology.
From henceforth, every single time that you hear about NADPHyou should be thinking biochemistry, has to be G6PD. Good. And
what if you're deficient of that enzyme. Who's your patientmost likely in G6PD deficiency. Well, maybe African. And really
it's an X-linked recessive, right, X-linked recessive.
07:21
So you need to have proper amounts of G6PD so that you can
then create the NADPH so that you can have proper reductionof your glutathione. So you can protect yourself against
the free radicals. Alright, okay. Now, is it possiblewith G6PD deficiency, usually when you think about G6PD
deficiency may I ask you; Are you going to be dealingwith this cell. What is this cell? A neutrophil. No. Usually
right you think G6PD deficiency Dr. Raj that is hemolytic anemia.
07:53
That is an RBC. Why are you even talking about it here? Because
when you have a patient and you're reading a stem of a question.
08:02
You are reading a chart of a patient. And they have hemolytic
anemia and they are susceptible to catalase positive organims.
08:11
This patient has G6PD deficiency. Okay, Dr. Raj I understand
that the patient ate fava beans and they ended up developinghemolytic anemia, I get that. Because now the RBC cannot
protect itself. But why is the patient susceptible to catalasepositive organisms? What's the name of that enzyme that we just
talked about that's responsible for creating superoxide?Take a look. NADPH oxidase. In G6PD deficiency, you cannot
produce any NADPH. If you can't produce NADPH, how can youform NADPH oxidase. Is that clear. You can't. Two cells that
are damaged in G6PD deficiency; RBC's, neutrophils.
09:06
No other condition is going to give you such a recurrent type
of behavior. So what about in chronic granulomatous disease,what did you learn about that in Immunology. Only a patient
that is susceptible to catalase positive organism.
09:23
There is no such thing as NADPH oxidase and RBC to protect the
RBC. Only the neutrophil. Three pathologies from this diagramand more information that I've given you here Fenton reaction
and myeloperoxidase. Spend time here, make sure that you'recompletely comfortable with everything that I've talked to
you about with enzymes and the biochemistry. The last littlepoint that I want you to make. I want you to go to the right
top. See the bacteria there. It's covered by chocolate. What?No, I'm being serious but it's covered by C3b. What am I
referring to? I'm not a huge fan of strawberries, okay.
10:07
But you put that strawberry in chocolate, I cannot get
enough. So, what is it that you're taking the bacteriathink of it as being a strawberry. In all seriousness, you
are taking the bacteria, you are dipping it into chocolatemaking it mighty tasty for the neutrophil. It's called an
opsonin. You see the bacteria. The chocolate is the C3b.
10:28
It's an opsonin also IgG. You are making it really really
tasty for the neutrophil to then bring about phagocytosis.
10:38
Is that clear? If it is, good. If it's a little bit too much,
digest this accordingly. Lot of good information.
10:47
All of this that I've talked about is high yield at any point in
time. In Pathology, Biochemistry, Immunology, questions will arise.

About the Lecture

The lecture Phagocytosis – Inflammation and Wound Repair by Carlo Raj, MD is from the course Cellular Pathology: Basic Principles.

Included Quiz Questions

The production of the free radical superoxide requires...?

NADPH oxidase

NADH

OH

GSH peroxidase

G6PD

Hemochromatosis causes destruction to cells in the body due to...?

Overproduction of free radicals

Oxidation of other metals

Deactivation of superoxide dismutase

Overproduction of HOCl

Rapid consumption of NADPH

Which disease is characterized by the failure of the phagosome to fuse with the lysosome?

Chediak-Higashi syndrome

Chronic granulomatous disease

NADPH oxidase deficiency

G6PD deficiency

Hemochromatosis

An African American patient presenting with symptoms of hemolytic anemia will most likely show all of the following characteristics EXCEPT....?

Failure of phagolysome to form

G6PD deficiency

Low levels of NADPH

Susceptibility to catalase positive organisms

Neutropenia

Which of the following molecules, if present on the surface of a bacterium, would make it more susceptible to phagocytosis?

C3b

NADPH

MPO

HOCl

GSSG

Author of lecture Phagocytosis – Inflammation and Wound Repair

Carlo Raj, MD

Customer reviews

(3)
4,3 of 5 stars

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Thank you

By Alan G. on 25. August 2017 for Phagocytosis – Inflammation and Wound Repair

Dr Raj makes everything more simple, it is a good effort you make to teach

Enjoyable

By Slavko M. on 20. July 2017 for Phagocytosis – Inflammation and Wound Repair

Very good, interesting and memorable lectures. Dr Raj presents complex topics in such a light way that makes it enjoyable to follow.

ARROGANCE.

By Jake Bryan C. on 20. January 2017 for Phagocytosis – Inflammation and Wound Repair

Great content. Very intelligent and elaborate lecturer. However, Dr. Raj sounds very arrogant, particularly when he delivers condescending remarks.

User Reviews

(3)
4,3 of 5 stars

5 Stars

2

4 Stars

0

3 Stars

1

2 Stars

0

1 Star

0

Thank you

By Alan G. on 25. August 2017 for Phagocytosis – Inflammation and Wound Repair

Dr Raj makes everything more simple, it is a good effort you make to teach

Enjoyable

By Slavko M. on 20. July 2017 for Phagocytosis – Inflammation and Wound Repair

Very good, interesting and memorable lectures. Dr Raj presents complex topics in such a light way that makes it enjoyable to follow.

ARROGANCE.

By Jake Bryan C. on 20. January 2017 for Phagocytosis – Inflammation and Wound Repair

Great content. Very intelligent and elaborate lecturer. However, Dr. Raj sounds very arrogant, particularly when he delivers condescending remarks.

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